Sweroside attenuates podocyte injury and proteinuria in part by activating Akt/BAD signaling in mice

波多辛 足细胞 尼福林 蛋白激酶B 体内 内分泌学 化学 内科学 药理学 生物 医学 细胞凋亡 蛋白尿 生物化学 生物技术
作者
Minjiang Huang,Yang Yang,Yuefu Chen,Li Yang,Sitao Qin,Lijun Xiao,Xuewen Long,Ke Hu,Yuxian Li,Huiming Ying,Yan Ding
出处
期刊:Journal of Cellular Biochemistry [Wiley]
卷期号:124 (11): 1749-1763 被引量:2
标识
DOI:10.1002/jcb.30484
摘要

Abstract In this study, we investigated the effects of sweroside on podocyte injury in diabetic nephropathy (DN) mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of DN to explore the effects of sweroside on proteinuria and podocyte injury in DN mice. In in vitro experiments, conditionally immortalized mouse podocytes were treated with high glucose and sweroside, and the protective effects of sweroside on podocyte injury were analyzed. In vitro, Akt/BAD pathways were detected using gene siRNA silencing assays and found to be involved in the protective roles of sweroside in high glucose‐mediated podocyte injury. In vivo, sweroside significantly decreased albuminuria in DN mice ( p < 0.01). periodic acid‐Schiff staining showed that sweroside alleviated the glomerular volume and mesangium expansion in DN mice. Consistently, western blot and reverse transcription‐polymerase chain reaction analyses showed that the profibrotic molecule expression in the glomeruli declined in sweroside‐treated DN mice. Immunofluorescent results showed that sweroside preserved nephrin and podocin expression, and transmission electron microscopy showed that sweroside attenuated podocyte injury. In DN mice, sweroside decreased podocyte apoptosis, and increased nephrin, podocin expression and decreased desmin and HIF1α expression. These results confirmed that sweroside ameliorated albuminuria, glomerulomegaly, and glomerulosclerosis in these mice. Experiments in vitro revealed that sweroside improved HG‐induced podocyte injury and apoptosis. Sweroside stimulated activation of the Akt/BAD pathway and upregulated Bcl‐2‐associated death promoter (BAD) and p‐Akt. Overall, sweroside protected podocytes from injury and prevented the progression of DN, providing a novel strategy for the treatment of DN.
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